Certain techniques, such as in analytical chemistry, require that components of a sample be ionized prior to analysis. Mass spectrometry (MS) is an example of such analytical techniques. Generally, MS encompasses a variety of instrumental methods of qualitative and quantitative analysis that enable ionized species of analytes (i.e., sample molecules of interest) to be resolved according to their mass-to-charge ratios. For this purpose, an MS system converts the components of a sample into ions, sorts or separates the ions based on their mass-to-charge ratios, and processes the resulting ion output (e.g., ion current, flux, beam, etc.) as needed to produce a mass spectrum. Typically, a mass spectrum is a series of peaks indicative of the relative abundances of charged components as a function of mass-to-charge ratio.
A typical MS system includes a sample inlet system, an ion source or ionization device, a mass analyzer, an ion detector, a signal processor, a readout/display means, and an electronic controller such as a computer. The MS system also includes a vacuum system to enclose the mass analyzer(s) in a controlled, evacuated environment. In addition to the mass analyzer(s), depending on design, all or part of the sample inlet system, ion source, and ion detector may also be enclosed in the evacuated environment. One broad class of ion sources, however, ionizes sample material at or near atmospheric pressure in a region necessarily distinct from the vacuum or low-pressure regions of the mass analyzer. Atmospheric-pressure ionization (API) thus requires a structural interface to transport ions produced in the atmospheric-pressure environment of the API source to the evacuated environment of the mass spectrometer. API techniques are particularly useful when it is desired to couple mass spectrometry with an analytical separation technique such as liquid chromatography (LC). For instance, the output or effluent from an LC column may serve as the sample source or input into an API interface. Typically, the effluent consists of a liquid-phase matrix of analytes and mobile-phase material (e.g., solvents, additives, matrix components, etc.).
Examples of API techniques include electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), atmospheric-pressure photoionization (APPI), and atmospheric-pressure matrix-assisted laser desorption/ionization (AP-MALDI). API techniques such as these are known and therefore need not be described in detail. As appreciated by persons skilled in the art, ESI is a desorption ionization technique characterized by the use of an electrically conductive electrospray needle. APCI is a gas-phase ionization technique characterized by the use of a corona discharge needle. APPI is characterized by the use of a photon source such as an ultraviolet (UV) lamp. AP-MALDI is characterized by the use of a pulsed laser beam and laser radiation-absorbing organic molecules.
Each technique typically employs an ionizing device extending into a chamber held at atmospheric pressure. The atmospheric-pressure chamber is physically separated from one or more vacuum or low-pressure regions of the mass spectrometer in which ion-guiding and mass-analyzing components reside. The ionizing device receives an analyte-bearing sample material from which the ionizing device produces a gaseous stream or spray that may comprise analyte ions, ion clusters, charged droplets, and neutral droplets. An inert nebulizing gas such as nitrogen (N2) may be utilized to assist in forming this sample spray. The resulting sample spray is directed through the interior of the atmospheric-pressure chamber to a sampling orifice that leads to the mass spectrometer. One or more electrical fields may be generated in the atmospheric-pressure chamber to guide the sample spray toward the sampling orifice.
Ideally in conventional techniques, only the analyte ions enter the mass spectrometer, and not the other components of the spray such as neutral solvated droplets. In addition to the above-mentioned optional nebulizing gas, a stream of an inert drying gas such as nitrogen may be introduced into the atmospheric-pressure chamber to assist in the evaporation of solvent and/or sweep the solvent away from the sampling orifice. The drying gas may be heated prior to introduction into the chamber. The drying gas may be introduced through an annular opening formed by a tube that is coaxial with the sampling orifice, in counter-flow relation to the spray as the spray approaches the sampling orifice. Alternatively, the drying gas may be introduced as a curtain in front of the sampling orifice.
A recurring problem in API techniques such as those noted above is the entry of unwanted droplets and other non-analytical material into the sampling orifice that serves as the entry into the evacuated regions of the mass spectrometer. Such unwanted components may degrade the performance of the mass spectrometer and/or the quality of the mass spectral data produced thereby through contamination, reduction in sensitivity, reduction in robustness, peak tailing, etc. These problems can be exacerbated as the flow rate of sample material introduced into the ion source is increased. As previously noted, the API ion source has conventionally been provided with a counterflow or a curtain of a heated, dry inert gas such as nitrogen to protect the sampling orifice by evaporating and blowing away the unwanted components. These previous approaches, however, have failed to adequately prevent the entry of unwanted components into the sampling orifice, and do not provide a sufficient degree of contact between the drying gas and the spray of sample material. In addition, in the previous approaches, desolvation of entrained sample cluster ions and evaporation of liquid droplets are incomplete, and the efficiency with which ions are extracted into the mass spectrometer is less than desirable. It is desirable to increase collisions of solvated ions or cluster ions prior to their entering the mass spectrometer to thereby increase the signal-to-noise (S/N) ratio.
In addition, the sampling orifice conventionally employed as the exit from the atmospheric-pressure ionization chamber to the mass spectrometer typically serves as the direct interface between the ionization chamber and the first stage of the mass spectrometer. This sampling orifice is typically the inlet of a small-diameter, long capillary that drops the fluid pressure from atmospheric down to about 1-20 mTorr. The inside diameter of the sampling orifice (and associated length of capillary) is determined by the pumping system provided with the ionization/mass spectrometry apparatus. Because it is not practical to pump gaseous fluid in these types of systems at a flow rate much greater than 60 CFM, the inside diameter of the sampling orifice is typically held to around 5 μm. The small diameter of the sampling orifice and its use for sampling the ion-bearing stream directly from the ionization chamber into the mass spectrometer result in a large portion of the ions produced in the ionization chamber not being collected in the sampling orifice for analysis by the mass spectrometer.
The foregoing problems attending conventional systems employing API interfaces may result in less than desirable performance parameters, such as low sensitivity, low S/N ratio, low ion signal strength, insufficient separation of analyte ions from liquid droplets and matrix background components, insufficient evaporation of liquid droplets, insufficient collisions of solvated ions or cluster ions and thus insufficient desolvation, and high chemical background. Accordingly, there continues to be a need for improving ionization techniques that require environments of higher pressure than, and thus an interface with, the associated low-pressure/vacuum analytical instrument receiving the as-produced ions such as a mass spectrometer.